tbuckley/cabot-search huggingface dataset:
Abstract P3-05-30: Survival after Development of Contralateral Breast Cancer
Authors: Hakyoung Kim, Hee Jeong Kim, Yoon Tae In, Seonok Kim, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn
Journal: Cancer Research (2023)

Abstract Purpose There are many studies reporting survival after development of contralateral breast cancer(CBC) but with inconsistent results. Also, many studies were based on European or North American population and few on Asian population. However, Korean breast cancer patients have different characteristics such as age distribution. Therefore, purpose of this study is to investigate whether development of CBC has influence on survival in Korean breast cancer population. Methods In this retrospective study, we included patients who were diagnosed with a first primary unilateral non-metastatic breast cancer at Asan Medical Center, Korea, between 1999-2013 followed through 2018. In this population, patients who delveloped CBC during the follow-up period were divided into the CBC cohort, and who did not into the non-CBC cohort. Survival of CBC cohort and non-CBC cohort was compared in the whole study population and in subgroup analysis by interval of CBC development, and breast cancer subtype. Results Over median follow-up of 107 months, 418 patients developed CBC out of 16,251 patients. Development of CBC did not influence overall survival or breast cancer-specific survival. In subgroup analysis by interval of CBC development, patients who developed CBC within one year after diagnosis of the first breast cancer had higher risk for overall death in CBC cohort (hazard ratio 2.58; 95% CI 1.28-5.18), and patients who developed CBC after one year showed no significant difference in survival compared with non-CBC cohort. In subgroup analysis by the subtype, patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative subtype for the first breast cancer showed higher risk for overall death in CBC cohort (hazard ratio 1.88; 95% CI 1.14-3.10) whereas patients with triple negative subtype for the first breast cancer showed lower risk for overall survival in CBC cohort (hazard ratio 0.42; 95% CI 0.19-0.95). Conclusion Development of CBC in Korean breast cancer patients did not have significant impact on survival. However, development of CBC early after diagnosis of first breast or having certain subtype of breast cancer may have affect on survival. Such information can be important information when counseling patients who are considering contralateral prophylactic mastectomy. Citation Format: Hakyoung Kim, Hee Jeong Kim, Yoon Tae In, Seonok Kim, Sae Byul Lee, Jisun Kim, Il-Yong Chung, Beom Seok Ko, Jong Won Lee, Byung Ho Son, Sei Hyun Ahn. Survival after Development of Contralateral Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-30.
Abstract P4-07-26: Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic breast cancer
Authors: Madeline Gough, Tashbib Khan, Kayden Kwah, Yaowu He, Gishan Ratnayake, Christopher Pyke, Cameron Snell, John Hooper, Thomas Kryza
Journal: Cancer Research (2023)

Abstract Introduction: CUB-domain containing- protein 1 (CDCP1) is a transmembrane receptor involved in the progression of several cancers. Recent studies demonstrate that CDCP1 is a rational target for the development of innovative targeted therapies for cancer including theranostics agents and antibody-drug conjugates. Objective/Methods: To determine the therapeutic potential of CDCP1 in breast cancer, we investigated its expression in multiple cohorts of breast cancer tissues by immunohistochemistry, as well as in various preclinical models including cell lines, primary cells and patient-derived xenografts using flow cytometry, western blot and immunofluorescence staining. Then, we evaluated the capacity of the CDCP1-targeting chimeric antibody ch10D7 to specifically accumulate in breast cancer lesions in in vivo preclinical models including patient-derived xenografts and breast cancer metastasis models. Finally, we determined the efficacy of the ch10D7-MMAE antibody-drug conjugate to kill breast cancer cells in vitro and breast tumours ex-vivo and in vivo. Results: The CDCP1 receptor is expressed at targetable level in a significant proportion of breast cancer cases with high/intermediate expression detected in ~30% of localized ER-positive cases, ~50% of metastatic ER-positive cases and &amp;gt;70% of Triple negative or HER2-positive cases. Similar proportion of expression was detected in cellular models. We demonstrated that ch10D7 antibody labelled with the radionucleotide Zircodium-89 specifically accumulates in breast cancer lesions in vivo allowing the detection of mammary-fat pad implanted patient-derived xenografts and of breast cancer metastasis by PET/CT imaging. Finally, we confirmed that the ch10D7-MMAE antibody-drug conjugate is very efficient at inducing cell death in vitro as well as controlling primary tumour and metastatic tumour burden in pre-clinical models, conferring a significant survival advantage compared to classical therapy. Conclusion: Our work demonstrates that CDCP1 is a potential target to detect and limit the progression of breast tumours and that biomolecules specifically recognising this receptor are promising agents which could improve survival of patients. Citation Format: Madeline Gough, Tashbib Khan, Kayden Kwah, Yaowu He, Gishan Ratnayake, Christopher Pyke, Cameron Snell, John Hooper, Thomas Kryza. Development of CDCP1-targeting antibody-drug conjugate for Triple negative and metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-26.
Abstract P6-01-45: Correlation of an immune-related 8-gene panel with the efficacy of neoadjuvant chemotherapy for breast cancer
Authors: Chun-Yu Liu, Chi-Cheng Huang, Yi-Fang Tsai, Ta-Chung Chao, Yen-Shu Lin, Chin-Jung Feng, Jiun-I Lai, Ji-Lin Chen, Yen-Jen Chen, Jen-Hwey Chiu, Chih-Yi Hsu, Ling-Ming Tseng
Journal: Cancer Research (2023)

Abstract Introduction: Neoadjuvant chemotherapy, one of systemic treatment of breast cancer, is employed for downstaging of inoperable tumor. Pathological complete response (pCR) after neoadjuvant chemotherapy is associated with good prognosis for breast cancer. The critical role of anti-tumor immune responses in conventional chemotherapy and targeted therapy has been reported. However, the pCR-associated immune genes are still ambiguous. Materials and Methods: Thirty-seven primary breast cancer patients receiving neoadjuvant chemotherapy as the first-line treatment for breast cancer were recruited in this VGH-TAYLOR study (NCT04626440). Total RNA of fresh tumor tissues was isolated and then reverse transcribed into cDNA. The Oncomine Immune Response Research Assay was employed for examination of immune-related gene expressions. In silico analyses were performed using the public databases, including Gene Expression Omnibus, Kaplan-Meier plotter, ROC Plotter, Cancer Therapeutics Response Portal, and The Cancer Genome Atlas. Results: Patients achieved a pCR were associated with lower tumor stage and HER2 expression. The next-generation sequencing-based analysis showed that the expression of eight genes were higher in tissues of patients with pCR than non-pCR, including KLRK1, IGJ, CD69, CD40LG, MS4A1, CD1C, KLRB1, and CA4. The 8-gene score was associated with better recurrence-free survival in patients receiving chemotherapy. Data from an ROC Plotter database showed that higher expressions of IGJ, CD69, and MS4A1 in patients respond to neoadjuvant chemotherapy compared to non-responders. In silico analysis revealed that the negative correlation between pCR-associated gene expressions and IC50 values suggesting the gene high expression was sensitive to the drugs. Moreover, the levels of pCR-associated gene were downregulated in breast tumor tissues and positively correlated with immune cell infiltrations. Conclusion: We identified eight immune genes which were associated with better prognosis and drug responses. The 8-gene score may serve as a prognostic marker for breast cancer patients who receiving neoadjuvant chemotherapy. Citation Format: Chun-Yu Liu, Chi-Cheng Huang, Yi-Fang Tsai, Ta-Chung Chao, Yen-Shu Lin, Chin-Jung Feng, Jiun-I Lai, Ji-Lin Chen, Yen-Jen Chen, Jen-Hwey Chiu, Chih-Yi Hsu, Ling-Ming Tseng. Correlation of an immune-related 8-gene panel with the efficacy of neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-45.
Abstract PD15-03: PD15-03 Incorporation of Repeated Core Needle Biopsy and Targeted Fine Needle Aspiration to Optimize Axillary Surgery After Neoadjuvant Chemotherapy in Node-positive Breast Cancer: A Prospective Feasibility Study
Authors: Siyu Wu, Jianwei Li, Ying Zhang, Na Hu, Guangyu Liu
Journal: Cancer Research (2023)

Abstract Background: It is of substantial importance to tailor axillary surgery after neoadjuvant chemotherapy (NAC) based on tumor biology and response to treatment. This study aimed to determine the accuracy of repeated core needle biopsy (RCNB) in breast to predict nodal response after NAC. Methods: Eligible patients with clip insertment into pathologically-proven positive node underwent RCNB during NAC. Targeted fine needle aspiration (TFNA) of clipped lymph node (CLN) was performed in a subset of patients after NAC. All patients ultimately underwent axillary surgery. RCNB and TFNA results were compared with surgical pathology. Results: Data from 189 eligible patients were analyzed. The overall axillary pCR was 57.1%. The false-negative rate (FNR) of RCNB across the whole cohort was 12.1% (95% CI, 5.3%–18.9%), and exploratory subgroup analysis revealed an excellent ability to predict the presence of residual nodal disease in estrogen receptor-positive breast cancer with a low FNR of 1.6% (95% CI, 0.0%–4.9%) (Table 1). Adopting a strategy where only patients with negative RCNB undergo targeted axillary dissection (TAD) would potentially reduce the FNR of TAD from 9.3% to 2.3%. Furthermore, combination of RCNB and TFNA demonstrated a FNR of 2.2% (95% CI, 0.0%–6.6%), and negative predictive value of 94.1% (95% CI, 81.6%–100.0%) (N = 87) (Table 2). The proposed algorithm based on RCNB and TFNA is helpful in optimizing axillary surgery by avoiding 25 unnecessary attempts as well as 2 false-negative cases in TAD and conferring 10 patients omission of axillary surgery. Conclusions: Combination of RCNB and TFNA allows for an accurate assessment of nodal response after NAC. These results may facilitate reliable identification of suitable candidates for de-escalation or elimination in axillary surgery. Table 1: Overall Cohort Diagnostic Accuracy of Repeated Core Needle Biopsy to Predict Nodal Response (N = 189) Abbreviations: ER, estrogen receptor; HER2, human epidermal factor receptor 2; NPV, negative predictive value; PPV, positive predictive value. Table 2. Diagnostic Accuracy of Repeated Core Needle Biopsy in Breast, Targeted Fine Needle Aspiration and the Combination in Cohort 2 (N = 87) Abbreviations: NPV, negative predictive value; PPV, positive predictive value; RCNB, repeated core needle biopsy; TFNA, targeted fine needle aspiration. Citation Format: Siyu Wu, Jianwei Li, Ying Zhang, Na Hu, Guangyu Liu. PD15-03 Incorporation of Repeated Core Needle Biopsy and Targeted Fine Needle Aspiration to Optimize Axillary Surgery After Neoadjuvant Chemotherapy in Node-positive Breast Cancer: A Prospective Feasibility Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-03.
Abstract P4-07-42: Intervention to Distant Metastatic Lesions in Patients with Breast Cancer
Authors: Hira Abidi, Serdar Ozbas, Beyza Ozcinar, Lutfi Dogan, Arda Isik, Emilia Diego, Priscilla F. McAuliffe, Ronald Johnson, Jennifer Steiman, Efe Sezgin, Atilla Soran
Journal: Cancer Research (2023)

Abstract INTRODUCTION Approximately one-fourth of patients presenting with early-stage breast cancer develop distant metastatic disease, a prominent cause of mortality. The role of metastasis-directed intervention is still uncertain in this cohort. The aim of this study is to evaluate whether intervention to metastatic lesions impacts overall survival (OS) and post-distant recurrence survival (PDRS), defined as survival after first occurrence of metastatic disease. METHODS Our prospectively maintained international multi-center database of patients diagnosed with distant recurrence was retrospectively reviewed. Patients initially presenting with stage I-III breast cancer and diagnosed with metastatic disease to the bone, liver or lung from 2014-2020 were divided into cohorts receiving intervention to their metastases (IM, n=180) versus no interventions to their metastases (NI, n=120). The characteristics of the patients were compared with X2 test. OS curves were calculated by Kaplan-Meier method and multivariable analysis by Cox regression. Statistical significance was set at p&amp;lt; 0.05. RESULTS No significant differences in OS and PDRS were noted between the two groups when comparing age at diagnosis, menopausal status, tumor histopathology, pathological stage, axillary lymph node involvement, and hormone receptor and HER2 status. However, median OS and PDRS were significantly longer for patients who received IM compared to those who did not. The hazard of death was 59% lower with IM than with NI for both OS (HR 0.59: 95% CI 0.42 – 0.83; p=0.002) and for PDRS (HR 0.59: 95% CI 0.42 – 0.84). On multivariable analysis, OS was improved among patients with IM, and among those with lung metastases, compared to liver and bone metastases. CONCLUSIONS Metastatic site intervention had both an OS and PDRS benefit in this cohort. In order to explore the potential for interventions to their metastases, patients who develop limited metastatic disease following initial breast surgery should be discussed at a multidisciplinary tumor board. Post-Distant Recurrence Survival in Patients with Breast Cancer Receiving Intervention to Metastatic Lesions (IM) Versus No Intervention (NI) Citation Format: Hira Abidi, Serdar Ozbas, Beyza Ozcinar, Lutfi Dogan, Arda Isik, Emilia Diego, Priscilla F. McAuliffe, Ronald Johnson, Jennifer Steiman, Efe Sezgin, Atilla Soran. Intervention to Distant Metastatic Lesions in Patients with Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-42.
Abstract PD6-02: PD6-02 Health-Related Quality of Life Trajectories and Predictors among Older Breast Cancer Survivors: A SEER-MHOS analysis
Authors: Eunkyung Lee, Sushantti Rupesh, Katia Ferdowsi, Robert Hines, Victoria Loerzel
Journal: Cancer Research (2023)

Abstract Health-related quality of life (HRQOL) is an important issue for breast cancer patients and clinicians in the treatment decision process. In addition, older women are more vulnerable due to pre-existing comorbidities and socioeconomic status. This study explored 10-year trajectories of HRQoL in older breast cancer survivors and their predictors using patient-reported outcomes data queried from the Surveillance, Epidemiology and End Results - Medicare Health Outcomes Survey (SEER-MHOS) data resources among Medicare beneficiaries. Older women diagnosed with breast cancer in 1998-2012 and who participated in the surveys before and at least once after diagnosis were included in the analysis. HRQOL was measured using SF-36/VR-12 questionnaire and summarized as Physical Component Summary (PCS) Score and Mental Component Summary (MCS) Score. Latent Class Growth Mixture Modeling was conducted to identify distinct groups of women with a similar trajectory of HRQOL. A total of 1089 women with breast cancer completed surveys an average of 2.6 times (range 2 - 19). The results showed that there were three latent classes of PCS trajectory: high-declining (46% of the sample), mid-declining (37%), and low-improving (17%). Two latent classes of MCS trajectory were identified: high-stable (76%) and low-declining (24%). The univariate analysis showed that age at diagnosis, body mass index, level of education, geographic region, tumor grade, tumor size, and the number of comorbidities were related to PCS and MCS scores. Multivariable multinomial logistic regression analysis identified the number of comorbidities as the most significant predictor for PCS score and level of education as the most significant predictor for MCS score. Future research needs to identify the most common comorbidities that influence HRQOL deterioration in older breast cancer survivors to develop interventions that better the physical HRQOL in patients. Also, interventions that target less educated, underserved patients to improve mental HRQOL. Citation Format: Eunkyung Lee, Sushantti Rupesh, Katia Ferdowsi, Robert Hines, Victoria Loerzel. PD6-02 Health-Related Quality of Life Trajectories and Predictors among Older Breast Cancer Survivors: A SEER-MHOS analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-02.
Abstract P5-12-05: Gestation and breast cancer in women with mutations in DNA repair genes: Is there any relationship?
Authors: María López-herrero lópez, Cristina Morales Estévez, Ana Armenta Triviño, Maria Jose Contreras, Maria Gómez Aguilera, Beatriz Rodriguez Alonso, Ignacio Porras, Juan de la Haba-Rodríguez, Enrique Aranda Aguilar
Journal: Cancer Research (2023)

Abstract Introduction: Women carrying mutations in reparative genes frequently ask about the safety of pregnancy or the use of fertility-promoting techniques. The evidence on gestation and breast cancer (BC), specifically in mutated BRCA, provides contradictory results1,3. On the one hand, there are studies that support the protective nature of pregnancy, while others show that gestation is a factor that promotes it1. Likewise, some point to differences in the association according to the type of mutation, BRCA1 or BRCA22. Objectives: To prove whether there is a relationship between pregnancy and BC in patients with mutations in DNA repair genes and to establish a solid knowledge base for counseling these patients in clinical practice. Patients and methods: We conducted an analytical, observational and retrospective study of 259 women with mutations in DNA repair genes, whether they had developed cancer or not, with different gestational histories in the Medical Oncology Service. The genes studied were: BRCA1and2, MUTYH, hMSH2, hMSH6,RAD51C,APC,CHECK2,ATM,PALB2,PTEN,BRIP1,ATM+RAD51D,BRCA1+NTHL1,CDKN2A,TP53,NF1,RAD51D. Results: The proportion of patients who develop cancer in the pregnant group is 46.9%. pregnant women is 46.9%, compared to 37.3% in nulliparous women ((χ²) =1.839, p= 0.171). We observed that the diagnosis of BC occurred before the age of 40 years in 40% of pregnant women, compared to 30% in nulliparous women. Likewise, we observed that from the third pregnancy onwards, the percentage of women suffering from BC is higher, with a peak in the fourth pregnancy (68.8% vs. 31.3%) (p=0.135) and that 51.3% of women whose first pregnancy was before the age of 30 years developed BC, compared to 38.6% in those whose first pregnancy was at a later age (X2=4.16, p=0.041). Finally, we observed that 80% of breast cancers developed after 10 years from the first birth. Conclusions: Considering our results, we cannot affirm that at present there is an association between gestation and BC in women with mutation in genes involved in DNA repair. Table: Cross table between cancer (Yes/No) and pregnancy (Yes/No) Citation Format: María López-herrero lópez, Cristina Morales Estévez, Ana Armenta Triviño, Maria Jose Contreras, Maria Gómez Aguilera, Beatriz Rodriguez Alonso, Ignacio Porras, Juan de la Haba-Rodríguez, Enrique Aranda Aguilar. Gestation and breast cancer in women with mutations in DNA repair genes: Is there any relationship? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-05.
Abstract PD5-07: PD5-07 Hepatic Leukemia Factor (HLF), a potential therapeutic target in triple negative breast cancer
Authors: Ibrahim BOUAKKA, Alicia TRAN-DIEN, Marine SIREROL, Aymeric Silvin, Fabrice Andre, Anna ROCCA
Journal: Cancer Research (2023)

Abstract The importance of the antitumor immune response in triple negative breast cancer (TNBC) is well established. We showed previously that the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease after neoadjuvant chemotherapy is associated with a better prognosis. By analyzing 99 pretreatment samples we discovered that the expression of the transcription factor Hepatic Leukemia Factor (HLF) in tumor cells is associated with lower infiltration of immune cells, leading to bad prognosis. Thereby, the aim of our project is to investigate the cellular and molecular mechanism regulated by HLF to better understand the tumor immune microenvironment, so we can develop better treatment options for patients with TNBC. Analysis of publicly available datasets of TNBC (METABRIC and TCGA) showed that tumors with low levels of HLF correlate with the upregulation of genes involved in biological processes associated with the regulation of immune response and in particular with neutrophils activation. Analysis of HLF expression patterns in these patients indicate that tumors presenting a mesenchymal profile exhibited higher HLF levels than the other TNBC subtypes. To elucidate the mechanism of this phenomenon regulated by HLF and his implication in anti-tumoral immune response, we developed several human TNBC cell lines knock-out or knock-down for our target gene using CRISPR/Cas9 editing technology. Comparison of the transcriptomes showed that the silencing of HLF in some mesenchymal TNBC cell lines lead to the upregulation of components involved in the attraction and activation of neutrophils, including CXCL8 (Neutrophil-activating peptide 1), a major cytokine directly responsible for the attraction of neutrophils in the tumor site. In vitro migration experiments supported these observations since purified blood circulating neutrophils have defective migration capacity that depends on the presence or absence of HLF. Finally, the co-culture of neutrophils with tumor cells silenced for HLF showed us, using a large panel of antibodies by spectral flow cytometry, an activated state of mature neutrophils. In conclusion, our study suggest that HLF plays a fundamental role in the regulation of genes involved in the control of tumoral immune microenvironment through the attraction and the activation of mature neutrophils. These findings have the potential for important implications since they suggest that HLF can be a potential target in treating TNBC. Citation Format: Ibrahim BOUAKKA, Alicia TRAN-DIEN, Marine SIREROL, Aymeric Silvin, Fabrice Andre, Anna ROCCA. PD5-07 Hepatic Leukemia Factor (HLF), a potential therapeutic target in triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD5-07.